| 1. |
- Granstam, Elisabet, 1963-, et al.
(författare)
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No findings of SARS-CoV-2 in conjunctival swabs from patients at an emergency outpatient ophthalmological healthcare facility in a Swedish county hospital : a cross-sectional study
- 2021
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Ingår i: BMJ Open Ophthalmology. - : BMJ Publishing Group Ltd. - 2397-3269. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background COVID-19 is caused by SARS-CoV-2. Virus has been found in conjunctiva of hospitalised patients with COVID-19. Conjunctivitis has also been reported as a presenting symptom of disease.Objective The aims of the study were to investigate the prevalence of SARS-CoV-2 in the conjunctiva and throat among patients presenting at the emergency outpatient ophthalmological healthcare facility at a county hospital along with investigating the seroprevalence of SARS-CoV-2 among staff at the department.Methods and Analysis Swabs from conjunctiva and throat of patients were analysed with real-time reverse transcriptase PCR (RT-PCR) for SARS-CoV-2. Blood samples for serological analysis were obtained from staff. A questionnaire was used to investigate symptoms associated with COVID-19 during the last 3 months as well as symptoms for which the patients were seeking ophthalmological healthcare.Results In total, 68 patients and 70 individuals from the staff were included in the study. Conjunctivitis was observed in 7% of patients. One patient, presenting with reduced visual acuity due to preretinal haemorrhage in the macula, was positive for SARS-CoV-2 in throat swab. Contact tracing was negative. All other RT-PCR tests were negative. Seropositivity for SARS-CoV-2 was found in 4% of staff.Conclusions Our study demonstrated low prevalence of SARS-CoV-2 among patients as well as low seroprevalence of SARS-CoV-2 IgG-antibodies among staff at the ophthalmological ward. The risk for contracting COVID-19 at the department was small. Follow-up investigation is planned.
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| 2. |
- Krifors, Anders, et al.
(författare)
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Long-lasting T-cell response to SARS-CoV-2 antigens after vaccination-a prospective cohort study of HCWs working with COVID-19 patients
- 2023
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 53:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vaccination against SARS-CoV-2 reduces the risk of hospitalisation and death, but vaccine-induced IgG antibodies against the spike protein (IgG S) decline over time. Less is known about the nature of the vaccine-induced T-cell response to SARS-CoV-2 antigens.METHODS: IgG antibodies against nucleocapsid protein (IgG N), IgG S, and T-cell response towards SARS-CoV-2 antigens were determined in samples taken between November 2020 and November 2021 from a cohort of healthcare workers at an Infectious Diseases Department. RT-PCR screening for SARS-CoV-2 was encouraged once every four weeks in addition to testing when symptomatic or identified through contact tracing. Vaccination data were collected at the end of the study.RESULTS: At inclusion, T-cell response to SARS-CoV-2 antigens was found in 10/15 (66.7%) of participants with a previous/current COVID-19 infection and in 9/54 (16.7%) of participants with no prior/current history of COVID-19 infection. All participants with complete follow-up (n = 59) received two doses of a SARS-CoV-2 vaccine during the study. All participants demonstrated detectable IgG (S) antibodies at the end of the study, in median 278 days (IQR 112) after the second vaccine dose. All but four participants displayed T-cell responses towards SARS-CoV-2 antigens. IgG S antibody levels correlated with time since the second vaccine dose. In addition, previous COVID-19 infection and the strength of the S1 T-cell response correlated with IgG S antibody levels. However, no correlation was demonstrated between the strength of the T-cell response and time since the second vaccine dose.CONCLUSION: COVID-19 vaccination induces robust T-cell responses that remain for at least nine months.
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| 4. |
- Pichtchoulin, Sara, et al.
(författare)
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Staphylococcus aureus bacteremia and cardiac implantable electronic devices in a county hospital setting : a population-based retrospective cohort study
- 2021
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 126:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Due to a high incidence of cardiac implantable electronic device-associated infective endocarditis (CIED-IE) in cases of Staphylococcus aureus bacteremia (SAB) and high mortality with conservative management, guidelines advocate device removal in all subjects with SAB. We aimed to investigate the clinical course of SAB in patients with a CIED (SAB+CIED) in a Swedish county hospital setting and relate it to guideline recommendations. Methods: All CIED carriers with SAB, excluding clinical pocket infections, in the County of Vastmanland during 2010-2017 were reviewed retrospectively. Results: There were 61 cases of SAB+CIED during the study period, and CIED-IE was diagnosed in 13/61 (21%) cases. In-hospital death occurred in 19/61 (31%) cases, 34/61 (56%) cases were discharged with CIED device retained, and 8/61 (13%) cases were discharged after device removal. Subjects dying during hospitalization were elderly and diseased. No events was seen if the CIED was removed. Among four discharged cases with conservatively managed CIED-IE one relapse occured. Among 30 cases discharged with retained CIED and no evidence of IE, 22/30 (73%) cases had an uneventful follow-up, whereas adverse events secondary to overlooked CIED-IE were likely in 1/30 (3%) cases and could not be definitely excluded in additionally 4/30 (13%) cases. Conclusions: During the study period, management became more active and prognosis improved. The heterogeneity within the population of SAB+CIED suggests that a management strategy based on an individual risk/benefit analysis could be an alternative to mandatory device removal.
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| 5. |
- Rasmusson, Annica J., et al.
(författare)
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Toll-like receptor 4 methylation grade is linked to depressive symptom severity
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric care. Methylation of 32 promoter-associated CpG sites in TLR1 to TLR10 was analysed using the Illumina Infinium Methylation EPIC BeadChip. Expression levels of 91 inflammatory proteins were determined by proximity extension assay. Statistical correlations between depressive state, TLR1-10 methylation and inflammatory proteins were investigated. Four additional cohorts were studied to evaluate the generalizability of the findings. In the discovery cohort, methylation grade of cg05429895 (TLR4) in blood was inversely correlated with depressive symptoms score in young adults. After correction for multiple testing, plasma levels of macrophage inflammatory protein 1 beta (MIP-1 beta/CCL4) were associated with both TLR4 methylation and depressive symptom severity. A similar inverse association between TLR4 methylation in blood and affective symptoms score was also found in a cohort of 148 both males and females (<40 years of age) from the Danish Twin Registry. These findings were not, however, replicated in three other external cohorts; which differed from the first two cohorts by a higher age and mixed ethnicities, thus limiting the generalizability of our findings. However, TLR4 methylation inversely correlated with TLR4 mRNA expression in the Danish Twin Study indicating a functional significance of methylation at this particular CpG. Higher depression scores in young Scandinavian adults was associated with decreased methylation of TLR4 in blood.
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| 6. |
- Welén, Karin, 1970, et al.
(författare)
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A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
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Tidskriftsartikel (refereegranskat)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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| 7. |
- Welen, Karin, et al.
(författare)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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